A rapid Diels-Alder approach to halogenated biaryl templates is described. These biaryl templates are available in two steps from the corresponding aromatic aldehydes. The scope of subsequent Suzuki couplings on the biaryl chlorides is explored. Good tolerance for both electron-donating and electron-withdrawing groups in the coupling process can be achieved. Further functionalization of the biaryl templates is described. Hydrogenation of the nitro moiety with concomitant removal of the benzyl ether yields the o-anilino, o-phenolic polyaryls. Selective reduction of the nitro group can be accomplished. Alternatively, the benzyl ether can be selectively removed under Lewis acidic conditions. The utilization of the Diels-Alder adducts for the synthesis of a series of chlorinated carbazoles via the Cadogan cyclization is also demonstrated. Finally, application of this technology to the total synthesis of siamenol, an anti-HIV agent, is reported.

Dipolar cylcoadditions with azides using a series of o-nitrophenylethynes and disubstituted alkynes were studied experimentally and computationally. Density functional theory computations reveal the steric and electronic parameters that control the regioselectivity of these cycloadditions. Several new substrates were predicted that would either give enhanced regiocontrol or invert the regiochemical preference. Experimentally, the alkynes were screened in the [3 + 2] cycloaddition with benzyl azide. Of the 11 alkynes screened experimentally, the acetylenes containing halogen substitution directly on the alkyne provided the highest levels of regioselectivity. These haloalkynes were also shown to tolerate variation of the azide moiety with continued good levels of regioselectivity in most cases. Diverse functional groups can be incorporated through the cycloaddition process and their subsequent orthogonal modification was demonstrated.

The dipolar cycloadditions of ortho-nitrophenyl alkynes with aryl nitrile oxides has been demonstrated. A range of substituents are tolerated on the alkyne. These reactions proceed with excellent levels of regioselectivity. Subsequent functionalization of the isoxazole scaffold has been demonstrated.

A new method to prepare halogenated biaryls is reported. These compounds are useful synthons which can smoothly be converted into other polyphenyl derivatives such as (VIII) and (IX) as well as to carbazoles like (XIII) and siamenol (XVII). -(NAFFZIGER, M. R.; ASHBURN, B. O.; PERKINS, J. R.; CARTER*, R. G.; J. Org. Chem. 72 (2007) 26, 9857-9865; Dep. Chem., Oreg. State Univ., Corvallis, OR 97331, USA; Eng.) -Jannicke 17-087

Highly Regioselective Nitrile Oxide Dipolar Cycloadditions with ortho-Nitrophenyl Alkynes. -For the success of the title reaction the ortho-nitro moiety and the sterically hindered mesityl group play an important role. -(MCINTOSH, M. L.; NAFFZIGER, M. R.; ASHBURN, B. O.; ZAKHAROV, L. N.; CARTER*, R. G.; Org. Biomol. Chem. 10 (2012) 46, 9204-9213, http://dx.